Adverse events and contradictory effects of benzodiazepine in a case with intellectual disability and challenging behaviour.

This study aims to contribute to the knowledge about lacking or contradictory effects of benzodiazepine on hyperaroused or aggressive behaviour in persons with intellectual disability (ID). We conducted a retrospective and natural case study in a person with mild ID and multiple adverse childhood experiences (ACE), using routine diary data consisting of 275 days including 113 consecutive days under benzodiazepine medication. The medication effects were documented as "calm / relaxed", "fretful / distressed" and "sleep / doze". Transitions between these were modelled using Markov chains. Differences in transitions were analysed using Chi-Square test for homogeneity. The results show a significantly reduced stability of mood and increased distressed behaviour under benzodiazepine. This is in line with reports about the effects of psychotropic medication in patients with ID and challenging behaviour. Besides other influences on unexpected medication effects, a possible dissociative identity disorder is discussed as an additional explanation.

The Digital Tree Drawing Test for Screening of Early Dementia: An Explorative Study Comparing Healthy Controls, Patients with Mild Cognitive Impairment, and Patients with Early Dementia of the Alzheimer Type.

The digital tree drawing test (dTDT) is a newly developed screening tool for the early detection of Alzheimer's disease. It is performed with a digitizing pen, recording each pen stroke with temporal and spatial precision. It was hypothesized that movement characteristics recorded during the painting process contribute to the identification of patients with mild cognitive impairment (MCI) and early dementia of the Alzheimer type (eDAT). The study population consisted of 187 participants (67 healthy controls, 64 MCI, and 56 eDAT patients) with a mean age of 68.6±10.6 years. Between-group comparisons of the dTDT-variables were conducted with analysis of variance. The diagnostic power of dTDT variables was analyzed with stepwise logistic regressions and areas under curve (AUC) of receiver operating control curves. Cognitively impaired persons used less colors and line widths and changed them less often than healthy subjects (p-values ≤0.05). Compared to control, eDAT patients had larger not-painting periods, were slower, and their pictures had less contrast, image size, and complexity (p-values ≤0.01). Logistic regression models of stepwise selected dTDT variables resulted in an AUC of 0.84 (95% confidence interval (CI) [0.79, 0.90], sensitivity = 0.78, specificity = 0.77) for discriminating healthy subjects from all cognitive impaired, an AUC of 0.77. (95% CI [0.69; 0.85], sensitivity = 0.56, specificity = 0.83) for discriminating healthy controls from MCI patients and an AUC of 0.90 (95% CI [0.84, 0.96], sensitivity = 0.86, specificity = 0.82) for discriminating controls from eDAT patients. The results suggest that digital recording of pen-stroke data during the drawing process can contribute to the screening of cognitive impaired patients.

Diagnostic value of digital clock drawing test in comparison with CERAD neuropsychological battery total score for discrimination of patients in the early course of Alzheimer's disease from healthy individuals.

The early detection of cognitive impairment or dementia is in the focus of current research as the amount of cognitively impaired individuals will rise intensely in the next decades due to aging population worldwide. Currently available diagnostic tools to detect mild cognitive impairment (MCI) or dementia are time-consuming, invasive or expensive and not suitable for wide application as required by the high number of people at risk. Thus, a fast, simple and sensitive test is urgently needed to enable an accurate detection of people with cognitive dysfunction and dementia in the earlier stages to initiate specific diagnostic and therapeutic interventions. We examined digital Clock Drawing Test (dCDT) kinematics for their clinical utility in differentiating patients with amnestic MCI (aMCI) or mild Alzheimer's dementia (mAD) from healthy controls (HCs) and compared it with the diagnostic value of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery total score. Data of 381 participants (138 patients with aMCI, 106 patients with mAD and 137 HCs) was analyzed in the present study. All participants performed the clock drawing test (CDT) on a tablet computer and underwent the CERAD test battery and depression screening. CERAD total scores were calculated by subtest summation, excluding MMSE scores. All tablet variables (i.e. time in air, time on surface, total time, velocity, pressure, pressure/velocity relation, strokes per minute, time not painting, pen-up stroke length, pen-up/pen-down relation, and CDT score) during dCDT performance were entered in a forward stepwise logistic regression model to assess, which parameters best discriminated between aMCI or mAD and HC. Receiver operating characteristics (ROC) curves were constructed to visualize the specificity in relation to the sensitivity of dCDT variables against CERAD total scores in categorizing the diagnostic groups. dCDT variables provided a slightly better diagnostic accuracy of 81.5% for discrimination of aMCI from HCs than using CERAD total score (accuracy 77.5%). In aMCI patients with normal CDT scores, both dCDT (accuracy 78.0%) and CERAD total scores (accuracy 76.0%) were equally accurate in discriminating against HCs. Finally, in differentiating patients with mAD from healthy individuals, accuracy of both dCDT (93.0%) and CERAD total scores (92.3%) was excellent. Our findings suggest that dCDT is a suitable screening tool to identify early cognitive dysfunction. Its performance is comparable with the time-consuming established psychometric measure (CERAD test battery).

Early Detection of Alzheimer's Disease Based on the Patient's Creative Drawing Process: First Results with a Novel Neuropsychological Testing Method.

Based on the knowledge of art therapy, we developed a new neuropsychological drawing test in order to identify individuals with mild cognitive impairment (MCI) as well as dementia patients and healthy controls (HC). By observing a variety of drawing characteristics of 92 participants with a mean age of 67.7, art therapy and dementia experts discriminate HC from MCI, early dementia of the Alzheimer-type (eDAT), and moderate dementia of the Alzheimer-type (mDAT) by the process analysis of tree drawings on a digitizing tablet. The art therapist's average categorical rating of healthy and MCI or demented individuals matched the clinical diagnosis by 88%. In a first small study, we analyzed interrater reliability, sensitivity, specificity, negative and positive predicted values of our tree drawing test (TDT) in comparison with the clock drawing test (CDT). Similar values of moderate interrater reliability were found for the TDT (0.56) as well as for the CDT (0.54). A significant high sensitivity of 0.9 within this binary impairment scale (HC versus impaired or demented) can be demonstrated. Substantial values for the specificity (0.67) could be obtained that however remain under a perfect value of the CDT (1.0). Considering 31 individuals that received the clinical diagnosis "impaired or demented" the TDT shows a higher recognition rate for the MCI group than the CDT. Furthermore in 8 of 12 borderline cases of clinical diagnosis, the outcome of the TDT diagnosis was consistent with the final clinical result.

Increased Diagnostic Accuracy of Digital vs. Conventional Clock Drawing Test for Discrimination of Patients in the Early Course of Alzheimer's Disease from Cognitively Healthy Individuals.

The conventional Clock Drawing Test (cCDT) is a rapid and inexpensive screening tool for detection of moderate and severe dementia. However, its usage is limited due to poor diagnostic accuracy especially in patients with mild cognitive impairment (MCI). The diagnostic value of a newly developed digital Clock Drawing Test (dCDT) was evaluated and compared with the cCDT in 20 patients with early dementia due to AD (eDAT), 30 patients with amnestic MCI (aMCI) and 20 cognitively healthy controls (HCs). Parameters assessed by dCDT were time while transitioning the stylus from one stroke to the next above the surface (i.e., time-in-air), time the stylus produced a visible stroke (i.e., time-on-surface) and total-time during clock drawing. Receiver-operating characteristic (ROC) curves were calculated and logistic regression analyses have been conducted for statistical analysis. Using dCDT, time-in-air was significantly increased in eDAT (70965.8 ms) compared to aMCI (54073.7 ms; p = 0.027) and HC (32315.6 ms; p < 0.001). In addition, time-in-air was significantly longer in patients with aMCI compared to HC (p = 0.003), even in the aMCI group with normal cCDT score (54141.8 ms; p < 0.001). Time-in-air using dCDT allowed discrimination of patients with aMCI from HCs with a sensitivity of 81.3% and a specificity of 72.2% while cCDT scoring revealed a sensitivity of 62.5% and a specificity of 83.3%. Most interestingly, time-in-air allowed even discrimination of aMCI patients with normal cCDT scores (80% from all aMCI patients) from HCs with a clinically relevant sensitivity of 80.8% and a specificity of 77.8%. A combination of dCDT variables and cCDT scores did not improve the discrimination of patients with aMCI from HC. In conclusion, assessment of time-in-air using dCDT yielded a higher diagnostic accuracy for discrimination of aMCI patients from HCs than the use of cCDT even in those aMCI patients with normal cCDT scores. Modern digitizing devices offer the opportunity to measure subtle changes of visuo-constructive demands and executive functions that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment in primary care.

Diagnostic Value of a Tablet-Based Drawing Task for Discrimination of Patients in the Early Course of Alzheimer's Disease from Healthy Individuals.

There is a considerable delay in the diagnosis of dementia, which may reduce the effectiveness of available treatments. Thus, it is of great interest to develop fast and easy to perform, non-invasive and non-expensive diagnostic measures for the early detection of cognitive impairment and dementia. Here we investigate movement kinematics between 20 patients with early dementia due to Alzheimer's disease (eDAT), 30 patients with amnestic mild cognitive impairment (aMCI), and 20 cognitively healthy control (HC) individuals while copying a three-dimensional house using a digitizing tablet. Receiver-operating characteristic (ROC) curves and logistic regression analyzes have been conducted to explore whether alterations in movement kinematics could be used to discriminate patients with aMCI and eDAT from healthy individuals. Time-in-air (i.e., transitioning from one stroke to the next without touching the surface) differed significantly between patients with aMCI, eDAT, and HCs demonstrating an excellent sensitivity and a moderate specificity to discriminate aMCI subjects from normal elderly and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer's disease from healthy individuals. Time-on-surface (i.e., time while stylus is touching the surface) differed only between HCs and patients with eDAT but not between HCs and patients with aMCI. Furthermore, total-time (i.e., time-in-air plus time-on-surface) did not differ between patients with aMCI and early dementia due to AD. Modern digitizing devices offer the opportunity to measure a broad range of visuoconstructive abilities that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment and dementia in primary care.